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Reduction of Liver Metastasis Stiffness Improves Response to Bevacizumab in Metastatic Colorectal Cancer.
Shen, Ying; Wang, Xiaohong; Lu, Junyan; Salfenmoser, Martin; Wirsik, Naita Maren; Schleussner, Nikolai; Imle, Andrea; Freire Valls, Aida; Radhakrishnan, Praveen; Liang, Jie; Wang, Guoliang; Muley, Thomas; Schneider, Martin; Ruiz de Almodovar, Carmen; Diz-Muñoz, Alba; Schmidt, Thomas.
Afiliação
  • Shen Y; Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
  • Wang X; Biochemistry Center, University of Heidelberg, 69120 Heidelberg, Germany; Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.
  • Lu J; Genome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
  • Salfenmoser M; Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
  • Wirsik NM; Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
  • Schleussner N; Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
  • Imle A; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
  • Freire Valls A; Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
  • Radhakrishnan P; Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
  • Liang J; Section of Molecular Immunology, Institute of Immunology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • Wang G; Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
  • Muley T; Thoracic Hospital, University Hospital Heidelberg, University Heidelberg, 69126 Heidelberg, Germany; Translational Lung Research Centre (TLRC) Heidelberg, Member of the German Centre for Lung Research (DZL), 69120 Heidelberg, Germany.
  • Schneider M; Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
  • Ruiz de Almodovar C; Biochemistry Center, University of Heidelberg, 69120 Heidelberg, Germany; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
  • Diz-Muñoz A; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Electronic address: diz@embl.de.
  • Schmidt T; Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. Electronic address: thomas.schmidt1@med.uni-heidelberg.de.
Cancer Cell ; 37(6): 800-817.e7, 2020 06 08.
Article em En | MEDLINE | ID: mdl-32516590
ABSTRACT
Tumors are influenced by the mechanical properties of their microenvironment. Using patient samples and atomic force microscopy, we found that tissue stiffness is higher in liver metastases than in primary colorectal tumors. Highly activated metastasis-associated fibroblasts increase tissue stiffness, which enhances angiogenesis and anti-angiogenic therapy resistance. Drugs targeting the renin-angiotensin system, normally prescribed to treat hypertension, inhibit fibroblast contraction and extracellular matrix deposition, thereby reducing liver metastases stiffening and increasing the anti-angiogenic effects of bevacizumab. Patients treated with bevacizumab showed prolonged survival when concomitantly treated with renin-angiotensin inhibitors, highlighting the importance of modulating the mechanical microenvironment for therapeutic regimens.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article